Leptin and its receptor are overexpressed in breast cancer tissue of postmenopausal Mexican-Mestizo women with obesity.

The aim of this study was to investigate the expression of leptin (LEP) and its receptor (LEPR) in breast cancer tissue of postmenopausal women with different body mass indexes (BMI), as well as the relationship of this expression with the rate of recurrence free survival (RFS). Leptin and LEPR expression, determined by immunohistochemistry, were studied in breast cancer tissues of 154 patients. Qualitative and semi-quantitative analysis of protein expression was performed by the H-Score method, through the ImageJ's IHC Profiler software. Kaplan-Meier survival analysis and log-rank statistic were used to estimate RFS differences. Protein expression of LEP, was significantly higher in women with overweight or with obesity, when compared to women with normal BMI (P = 0.032 and P = 0.013, respectively). We also observed a significantly higher expression of LEPR in breast tumor cells of women with obesity (58.8%), when compared to women with normal BMI (32.7%) (P = 0.007). Five-year survival rate, regarding LEPR expression, was 82.4% when positive and 94% when negative (P = 0.024). In the Cox proportional-hazards regression model, LEPR expression represented a risk factor for disease recurrence after adjustment for confounding factors (HR = 4.67; 95% CI: 1.13-19.31; P = 0.033). In conclusion, postmenopausal women with obesity and breast cancer present higher LEP and LEPR expression in breast tumors, when compared to women with normal BMI. Independently from BMI, women with tumors LEPR positive have worst RFS, when compared to women with tumors LEPR negative.

Different body mass indexes and their relation to prognosis of early-stage breast cancer in postmenopausal Mexican-Mestizo women.

It has been suggested that obesity increases the incidence of metastatic breast tumors, resulting in higher rates of recurrence, and increased mortality; for that reason, the aim of this study was to investigate if different body mass indexes modified the clinicopathologic characteristics of breast cancer; as well as, the recurrence-free survival in postmenopausal Mexican-Mestizo women. Two hundred twenty postmenopausal women with operable breast cancer were included. A structured questionnaire was applied to explore the existence of potential risk factors. Body mass index (BMI) was determined in each case and patients were grouped in accordance to their BMI in: normal weight, overweight, or obesity. Kaplan-Meier survival analysis and log-rank statistic were used to estimate recurrence-free-survival differences. Hormonal receptor(+)/HER2(-) was the most frequent breast cancer in all groups. Overweight women presented a statistically significant increased risk of this molecular subtype, with an odds ratio (OR) = 5.57; 95% confidence interval (CI) = 1.54-24.86; P = .004)). In addition, the triple-negative subtype was more frequent in women with a normal BMI in comparison to women with overweight (P = .016) or women with obesity. The heterogeneity in cancer subtypes regarding BMI was observed.

Overweight and obesity in men with prostate cancer do not constitute risk factors for biochemical recurrence.

AIM: To investigate if overweight and obesity were associated with a higher degree of biochemical recurrence (BCR) after radical prostatectomy, in Mexican men with prostate cancer (PCa). METHODS: We included 180 men with PCa, who underwent radical prostatectomy (RP). Body mass index (BMI) was determined and the degree of PCa aggressiveness was established according to the D'Amico classification. Postoperative follow-up of all patients was performed with PSA quantification every/6 weeks after surgery and then at 3-month intervals for 1 year, followed every/6 months for 5 years. Postoperative BCR was defined as two consecutive increases in PSA levels ≥0.4 ng/mL, after RP. RESULTS: Sixty eight percent of the patients presented overweight or obesity. We found that only intermediate/high risk patients presented an increased risk factor for BCR-free survival (HR = 4.39; 95% CI = 1.74-11.24; p = 0.002). The median follow-up of all men has been 7.9 years and no significant differences in BCR-free survival time has been observed between the BMI groups. CONCLUSIONS: The overweight and obesity do not represent a risk factor to present BCR after RP for PCa. However, an intermediate/high risk, according to the D'Amico's classification, constitutes a risk factor to present BCR after radical prostatectomy, which is not related to the BMI.

Serum concentrations of apelin-17 isoform vary in accordance to blood pressure categories in individuals with obesity class 3.

Background: The aim of this study was to investigate if serum concentrations of apelin-36, apelin-17, apelin-13 or apelin-12 were different in obesity class 3 individuals with hypertension, when compared to those without hypertension (normal or high-normal).Subjects and Methods: Twenty six individuals with obesity class 3-related hypertension and thirty three individuals without hypertension, who were divided in individuals with normal (n = 23) or with high-normal (n = 10) blood pressure (BP) were analyzed. All individuals presented obesity class 3, without diabetes mellitus. Measurements of all apelin isoforms were performed using enzyme-linked immunosorbent assay kits. Analysis of differences between groups of Apelin isoform concentrations was performed by a One-way ANOVA, with a Tukey test post hoc.Results: The individuals of the hypertensive group presented a slightly lower serum concentration of all apelin isoforms, but these differences were not statistically significant. These results were more evident when the group of patients without hypertension were divided based in normal and high-normal BP, observing that apelin-17 isoform were higher in individuals with high-normal BP in comparison to subjects with normal BP (P = 0.018); concentrations were also higher when compared to subjects with hypertension (P = 0.004).Conclusions: To our knowledge, this is the first study regarding the differences of apelin-17 isoform concentrations in individuals pertaining to different categories of BP, who presented obesity class 3. The group of patients that presented hypertension showed a lower concentration of all isoforms. This observation could be due to the fact that these patients were taking antihypertensive medication.

Duplication of SOX9 associated with 46,XX ovotesticular disorder of sex development.

RESEARCH QUESTION: The purpose of the present study was to investigate whether ten unrelated SRY-negative individuals with this sex differentiation disorder presented a double dose of SOX9 as the cause of their disease. DESIGN: Ten unrelated SRY-negative 46,XX ovotesticular disorder of sexual development (DSD) subjects were molecularly studied. Multiplex-ligation dependent probe amplification (MLPA) and quantitative real-time PCR analysis (qRT-PCR) for SOX9 were performed. RESULTS: The MLPA analysis demonstrated that one patient presented a heterozygous duplication of the entire SOX9 coding region (above 1.3 value of peak ratio), as well as at least a ~ 483 kb upstream duplication. Moreover, no duplication of other SOX9 probes was observed corresponding to the region between -1007 and -1500 kb upstream. A qRT-PCR analysis showed a duplication of at least -581 kb upstream and ~1.63 kb of the coding region that encompasses exon 3. The limits of the duplication were mapped approximately from ~71539762 to 72122741 of Chr17. No molecular abnormalities were found in the remaining nine patients. CONCLUSION: This study is thought to be the first report regarding a duplication of SOX9 that is associated with the presence of 46,XX ovotesticular DSD, encompassing at least -581 kb upstream, and the almost entire coding region of the gene.

Complete sequence of the ATP6 and ND3 mitochondrial genes in breast cancer tissue of postmenopausal women with different body mass indexes.

Due to the fact that mitochondrial defects and oxidative stress have been related with obesity and breast cancer is more aggressive in women with obesity, we investigated if postmenopausal Mexican-Mestizo women with breast cancer presented somatic mutations in the sequence of the ATP6 and/or ND3 genes. Twenty one postmenopausal Mexican-Mestizo women with breast cancer who underwent mastectomy or breast conserving surgery were studied. Height and weight were used to calculate body mass index. DNA from tumor tissue samples and blood leukocytes was amplified by polymerase chain reaction and sequenced the ATP6 and ND3 mitochondrial genes. Ages ranged from 46 to 82. According to World Health Organization criteria among the 21 women, 7 had a normal BMI, 7 were overweight and 7 had obesity. In regard to the molecular study, after sequencing the coding region of ATP6 and ND3 genes of the DNA obtained from both leukocytes and tumor tissue, we did not find somatic mutations. All of the changes that we found in both genes were polymorphisms: in ATP6, we identified in ten patients 3 non-synonymous nucleotide changes and in ND3 we observed that six patients presented polymorphisms, three of them were synonymous and two non-synonymous. To our knowledge, this constitutes the first report where the complete sequence of the ATP6 and ND3 genes has been analyzed in postmenopausal Mexican-Mestizo women with breast cancer and diverse BMI. Our results differ with those reported in Caucasian and Asian populations, possibly due to ethnic differences.

Eating behavior and psychological profile: associations between daughters with distinct eating disorders and their mothers.

BACKGROUND: Associations of eating behaviors and psychological profile between mothers and daughters with eating disorders exist, but it is important to dissect the influence of the mother in each specific disorder since all eating disorders must be seen or treated not as one entity. The aim of the present study was to evaluate the association of eating behavior and psychological profile between mothers and daughters with different eating disorders and a control group. METHODS: The study group included young girls with anorexia nervosa (AN, n = 30), bulimia nervosa (BN, n = 30), binge eating disorder (BED, n = 19), and a control group of women (Non-ED, n = 54) together with their mothers. BMI was calculated for dyads and Eating Disorder Inventory, Beck Depression Inventory, Beck Anxiety Inventory, Toronto Alexithymia Scale and Three-Factor Eating Questionnaire were applied. The differences between dyads were tested by Student's t test and Pearson's correlation was used to study the association between BMI, variables of eating behavior and psychological profile in each dyad. RESULTS: The study found significant inverse correlations between the AN dyad; some correlations between the BN dyad, and the highest positive correlations exist in BED dyad, especially in eating behavior. Finally, between the control dyads, low but significant correlations were found in the majority of cases. CONCLUSIONS: The study concluded that the associations between mothers and daughters with distinct eating disorders varied depending on the specific diagnosis of the daughter, indicating it is necessary to analyze them individually, given that there may be different implications for treatment.

Genetic variants in ATP6 and ND3 mitochondrial genes are not associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.

Mitochondrial defects have been related to obesity and prostate cancer. We investigated if Mexican-Mestizo men presenting this type of cancer, exhibited somatic mutations of ATP6 and/or ND3.Body mass index (BMI) was determined; the degree of prostate cancer aggressiveness was demarcated by the Gleason score. DNA from tumor tissue and from blood leukocytes was amplified by the polymerase chain reaction and ATP6 and ND3 were sequenced. We included 77 men: 20 had normal BMI, 38 were overweight and 19 had obesity; ages ranged from 52 to 83. After sequencing ATP6 and ND3, from DNA obtained from leukocytes and tumor tissue, we did not find any somatic mutations. All changes observed, in both genes, were polymorphisms. In ATP6 we identified, in six patients, two non-synonymous nucleotide changes and in ND3 we observed that twelve patients presented non-synonymous polymorphisms. To our knowledge, this constitutes the first report where the complete sequences of the ATP6 and ND3 have been analyzed in Mexican-Mestizo men with prostate cancer and diverse BMI. Our results differ with those reported in Caucasian populations, possibly due to ethnic differences.

Triallelic digenic mutation in the prokineticin 2 and GNRH receptor genes in two brothers with normosmic congenital hypogonadotropic hypogonadism.

UNLABELLED: Purpose/aim of the study: To date, different genes have been identified as responsible for the presence of normosmic congenital hypogonadotropic hypogonadism (nCHH). Herein, we report the molecular findings regarding the analysis of PROK2, in two brothers with nCHH. SUBJECTS AND METHODS: Two siblings with nCHH, in whom mutations in GNRHR, PROKR2 and FGFR1 had been investigated previously, as well as their family were studied. DNA was amplified by PCR and sequenced for the PROK2 gene. Controls were analyzed by restriction fragment-length polymorphism. The structure of PROK2 and its mutant protein were compared using a protein molecular model. RESULTS: Both affected siblings exhibited a heterozygous p.R117W mutation in PROK2, while their mother was a heterozygous carrier and their father, an unaffected brother and their sister were homozygous wild type. Besides, both patients presented a homozygous p.E90K mutation in GNRHR that had been previously reported. CONCLUSIONS: We found a novel mutation in PROK2 in two siblings in whom a mutation in the GNRHR gene had been previously reported.

(-)-epicatechin treatment did not modify the thermogenic pathway in the gastrocnemius muscle of male rat offspring obeses by programming.

The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd (p < 0.036, MO vs. MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group (p = 0.006).No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.

Experience of an eating disorders out-patient program in an internal medicine hospital.

PURPOSE: The aim of this study was to develop a successful low budget out-patient program, in an internal medicine hospital, for patients presenting eating disorders in an emerging nation. METHODS: A total of 144 patients were included in a 6 month intervention centered in medical support, with fortnightly medical consultations, monthly counseling by a nutritionist and by a psychiatrist and three psycho-educational courses. The Three Factor Eating Questionnaire and the Eating Disorders Inventory-2 were performed at the beginning and at the end of the study. RESULTS: After 6 months, more than half of the patients who completed the intervention were on remission. Substantial improvement was observed regarding the scores of both instruments after completion of the program. CONCLUSIONS: The outcome of this study compares favorably to previous published data of more intensive programs. These results were obtained having little infrastructure, a low budget and limited human resources, making this a suitable eating disorders program for emerging nations.

(-)-Epicatechin increases apelin/APLNR expression and modifies proteins involved in lipid metabolism of offspring descendants of maternal obesity.

Several studies have shown the beneficial effects of (-)-epicatechin (Epi) in metabolic profile and that this flavanol is a biased ligand of the apelin receptor. The apelinergic system is expressed in adipocytes and has been related to obesity and metabolic disorders. The study aim was to evaluate the effect of Epi on apelin, on its receptor and on proteins involved in lipolysis, lipogenesis, and adipogenesis in the retroperitoneal adipose tissue of male rats descended from obese mothers. We evaluated the effect of Epi in the retroperitoneal adipose tissue of four groups of male offspring, analyzing mRNA expression and protein levels of apelin and its Apj receptor. We also analyzed, by Western Blot, the levels of AMPKα, ACC, C/EBPα, ATGL, Fas, and FABP4 of the AP2 proteins. Epi significantly elevated apelin mRNA expression and protein levels as well as its Apj receptor. Besides, the flavanol significantly promoted AMPKα phosphorylation with the concomitant reduction of Fas, and the increase of the ATGL protein. In contrast, there was an increase in the inactive phosphorylated form of ACC and a decrease in the phosphorylated active form of C/EBPα. Similarly, Epi treatment induced a reduction in the fatty acid-binding protein 4 in the C+Epi and MO+Epi groups. In conclusion, Epi increases the expression of the apelinergic system and the active phosphorylated form of AMPKα; likewise, it modifies the expression level or active form of proteins involved in lipolysis, lipogenesis and adipogenesis in the retroperitoneal adipose tissue of male offspring of obese mothers.

High knowledge about obesity and its health risks, with the exception of cancer, among Mexican individuals.

Mexico has the second biggest prevalence in the world of obese adults (30%). We conducted a survey to determine knowledge concerning obesity co-morbidities. Three groups were surveyed with a questionnaire divided into three sections: demographic characteristics; knowledge and awareness in relation to obesity being a disease; causes of obesity and the health risks it represents; weight auto-perception and the subject's personal experiences regarding weight. In all groups we found high knowledge regarding that obesity is a disease and the causes of its development, as well as that it greatly increases the risk of presenting type 2 diabetes, high blood pressure and knee osteoarthritis. However, in all groups, there was a gap in knowledge regarding the risk obesity poses for the development of breast and colon cancer. Aggressive health promotion campaigns concerning obesity, which have been implemented recently in Mexico, must emphasize cancer as a potential outcome for obese patients.

(-)-Epicatechin improves body composition of male rats descendant of obese mothers postnatally fed with a high-fat diet.

A combination of maternal obesity and high-fat diet (HFD) in offspring postnatal life has deleterious effects, and (-)-epicatechin (Epi) treatment can reverse these adverse effects. To investigate whether Epi administration can modify fat mass, muscle mass, and bone mass in male rats descended from obese mothers, fed postnatally on an HFD. Male offspring of mothers fed with control diet formed the control group (C), control group with high-fat diet (CHF), and control group with high-fat diet + epicatechin (CHF + Epi). Male offspring of maternal obesity formed the group with control diet (MO), maternal obesity group with high-fat diet (MOHF), and maternal obesity group with high-fat diet + epicatechin (MOHF + Epi). We measured total fat and weight of visceral adipose tissue by dissection and by dual-energy x-ray absorptiometry scanning body composition. Epicatechin diminished total and visceral pads fat of male offspring of CHF + Epi and MOHF + Epi groups versus to male offspring of CHF and MOHF groups. Besides, epicatechin increased lean mass in CHF + Epi and MOHF + Epi groups, but these changes were not significant. Total body mineral density of the male offspring of CHF, MOHF, and MOHF + Epi groups was significantly higher versus male offspring of C and MO groups. Obesity programming model plus a high-fat postnatal diet presents higher visceral adipose tissue, decreased lean mass, and modified body mineral density when compared with a direct obesity model and its controls. Epicatechin treatment improved body composition; however, it was not able to induce similar values as presented by the controls.

Early preoperative progressive pneumoperitoneum for a symptomatic giant abdominal incisional hernia.

INTRODUCTION AND IMPORTANCE: Early preoperative progressive pneumoperitoneum (PPP) is a technique that helps large eventrations with loss of domain to reintroduce protruded organs. However, a standardized technique has not been developed. This technique has been proved in elective patients, but the evidence is scarce in patients with a high risk of incarceration/strangulation. CLINICAL FINDINGS AND INVESTIGATIONS: We present a 61-year-old patient with history of a thoracoabdominal aneurysm repair, developed a massive incisional hernia with loss of domain. At admission, he presented with abdominal pain and inability to reduce the hernia by himself, however it reduced after clinical examination. Aortic syndromes were excluded. INTERVENTIONS AND OUTCOME: After a multidisciplinary meeting, early PPP was initially performed. Later he was taken to surgery and admitted in the ICU to prevent abdominal hypertension. Medical complications resolved within 14 days. The patient did not report long-term complications. RELEVANCE AND IMPACT: PPP is a technique that pursues the prevention of abdominal hypertension syndrome in patients with large hernias with loss of domain electively. For patients with high risk of hernia complications, the evidence is limited regarding the applicability of early PPP. A multidisciplinary team can improve decision making and therefore reduce the risk of long-term complications. We show a case where PPP was performed in an acute painful, reducible hernia with a high risk of incarceration, showing that this approach can be an option for acutely ill patients.

Sera from women with different metabolic and menopause states differentially regulate cell viability and Akt activation in a breast cancer in-vitro model.

Obesity is associated with an increased incidence and aggressiveness of breast cancer and is estimated to increment the development of this tumor by 50 to 86%. These associations are driven, in part, by changes in the serum molecules. Epidemiological studies have reported that Metformin reduces the incidence of obesity-associated cancer, probably by regulating the metabolic state. In this study, we evaluated in a breast cancer in-vitro model the activation of the IR-ß/Akt/p70S6K pathway by exposure to human sera with different metabolic and hormonal characteristics. Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-κB activation. We demonstrated that MCF-7 cells represent a robust cellular model to differentiate Akt pathway activation influenced by the stimulation with sera from obese women, resulting in increased cell viability rates compared to cells stimulated with sera from normal-weight women. In particular, stimulation with sera from postmenopausal obese women showed an increase in the phosphorylation of IR-ß and Akt proteins. These effects were reversed after exposure of MCF-7 cells to sera from postmenopausal obese women with insulin resistance with Metformin treatment. Whereas sera from women without insulin resistance affected NF-κB regulation. We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance. Our results suggest a possible mechanism in which obesity-mediated serum molecules could enhance the development of luminal A-breast cancer by increasing Akt activation. Further, we provided evidence that the phenomenon was reversed by Metformin treatment in a subgroup of women.

Increased FNDC5/IRISIN protein expression in breast cancer tissue is associated with obesity in postmenopausal women.

AIM: To analyse the fibronectin type III domain containing 5 (FNDC5)/irisin expression in tumour tissue of postmenopausal women presenting breast cancer and different body mass indexes (BMIs), proposing that obesity deregulates the expression of FNDC5/irisin at the breast tumour level. In addition, we investigated if different breast cancer cell lines are capable to synthesise this protein. METHODS: A total of 150 postmenopausal women (50 with a normal BMI, 50 presenting overweight and 50 having obesity) diagnosed with operable breast cancer were included. FNDC5/irisin expression was determined by immunohistochemistry or by immunocytochemistry. Qualitative analysis of protein expression was performed by the H-Score method, through ImageJ's IHC Profiler software. Statistical analyses were carried out using STATA V.14.0 (Texas, USA); p value<0.05 was accepted as statistically significant. Statistical power of the study was >80% with a p<0.05. RESULTS: FNDC5/irisin expression in breast cancer tissue of postmenopausal women with obesity was significantly increased when compared with FNDC5/irisin expression in women with a normal BMI (p=0.001). Furthermore, three breast cancer cell lines studied were capable to synthesise and express FNDC5/irisin, being the BT-474 cell line the one that exhibited the highest intensity of expression. CONCLUSIONS: Our results confirm that women with breast cancer and obesity exhibit an increased irisin expression in their tumorous tissue compared with women with breast cancer and normal BMI. Likewise, in vitro breast cancer cell lines have the capacity to synthesise and express FNDC5/irisin, without any extracellular stimuli, however the microenvironment surrounding these cells in vivo participates in its regulation.

Adiponectin and adiponectin receptor 1 expression proteins levels are modified in breast cancer in postmenopausal women with obesity.

AIM: To analyse the expression of adiponectin (ADIPOQ), and its receptors ADIPOR1 and ADIPOR2, in breast cancer tissue of postmenopausal women with different body mass indexes (BMIs). SUBJECTS AND METHODS: One hundred and fifty postmenopausal Mexican-Mestizo women with breast cancer were included. BMI was determined in each case. To carry out qualitative and semiquantitative assessments of protein expression by immunohistochemistry, the H-Score method was used, through ImageJ's IHC Profiler software. Statistical power of the study was >80% with a p<0.05. RESULTS: Fifty women had a normal BMI, 50 presented overweight and 50 had obesity. The expression of ADIPOQ in breast cancer tissue of postmenopausal woman with normal BMI was higher in comparison to women with overweight or with obesity (p=0.002 and p<0.001, respectively). Furthermore, the expression of ADIPOR1 in breast cancer tissue of postmenopausal women with normal BMI was significantly lower when compared with women with overweight or with obesity (p=0.005 and p<0.001, respectively). Meanwhile, the expression of ADIPOR2 in breast cancer tissue, in the cytoplasm, was similar in all groups studied. CONCLUSIONS: We found that women with overweight or obesity had a lower expression of ADIPOQ and a higher ADIPOR1 expression in breast cancer tissue, when compared with women with a normal BMI.

Reproductive axis function and gonadotropin microheterogeneity in a male rat model of diet-induced obesity.

Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet. Long-term (180 days), high-fat feeding rats exhibited a metabolic profile compatible with insulin resistance and metabolic syndrome; they concomitantly showed decreased intrapituitary and serum LH concentrations, low serum testosterone levels, and elevated serum 17beta-estradiol concentrations. A fall in biological to immunological ratio of intrapituitary LH was detected in 180 days control diet-treated rats but not in high-fat-fed animals, as assessed by a homologous in vitro bioassay. Chromatofocusing of pituitary extracts yielded multiple LH charge isoforms; a trend towards decreased abundance of more basic isoforms (pH 9.99-9.0) was apparent in rats fed with the control diet for 180 days but not in those that were fed the diet enriched in saturated fat. It is concluded that long-term high-fat feeding alters the function of the pituitary-testicular axis, resulting in hypogonadotropic hypogonadism. The alterations in LH function found in these animals might be subserved by changes in hypothalamic GnRH output and/or sustained gonadotrope exposure to an altered sex steroid hormone milieu, representing a distinctly different regulatory mechanism whereby the pituitary attempts to counterbalance the effects of long-term obesity on reproductive function.

The gonadal expression pattern of lipocalin­2 and 24p3 receptor is modified in the gonads of the offspring of obese rats.

Obesity represents a global health and economic burden, affecting millions of individuals worldwide. This pathology is associated with a chronic low­grade inflammatory state that is partially responsible for the development of other cardiometabolic complications. Clinical studies have reported an association between high circulating levels of lipocalin­2 (Lcn2) and increased body weight. Additionally, there is scientific evidence demonstrating the impact of maternal obesity on fetal programming. The latter and the fact that the authors previously found that Lcn2 and its receptor (24p3R) are expressed in the gonads of wild­type rats, led to the analysis of their mRNA profile and cellular localization in gonads collected from the offspring of obese rats at 21 days postconception (dpc), and 0, 2, 4, 6, 12, 20 and 30 days postnatal (dpn) in the present study. Semi­quantitative PCR revealed a statistically significant downregulation of Lcn2 and 24p3R mRNA at 21 dpc in the ovaries (P<0.01) and testicles (P<0.001) of the offspring of obese mothers. At 30 dpn, the relative expression of Lcn2 mRNA decreased significantly in the ovaries of the experimental group (P<0.05), while Lcn2 mRNA expression was not detectable in testicles. Regarding 24p3R, its mRNA was only significantly decreased at 21 dpc in ovaries of pups of obese mothers. At 30 dpn, the change in females was not significant. Conversely, in testicles, 24p3R mRNA levels increased slightly in the experimental group at 30 dpn. The Lcn2 protein signal was less intense in gonadal tissue sections from 30 dpn offspring of obese rats (P<0.001), whereas the 24p3R signal was downregulated in ovaries (P<0.001) and slightly upregulated in testicles. It was concluded that maternal obesity changes the expression of Lcn2 and 24p3R in the gonads of the offspring of obese rats, possibly through fetal programming. The consequences of this dysregulation for the offspring's gonadal function remains to be determined.